title: Comparative pharmacokinetics of paclitaxel after oral administration of Taxus yunnanensis extract and pure paclitaxel to rats.
abstract: Taxus yunnanensis (T. yunnanensis) is endemic to China and has been used in traditional medicine for the treatment of cancer, diabetic ailments and others. Paclitaxel is a representative antitumor compound in the Taxus species. The pharmacokinetic behavior of paclitaxel after oral administration of the crude extract of T. yunnanensis has not been investigated. This study attempts to compare the pharmacokinetics of paclitaxel after an oral administration of the crude extract of the twigs and leaves of T. yunnanensis and pure paclitaxel. A UPLC and a UPLC/MS/MS analysis method were developed for the determination of paclitaxel in T. yunnanensis extract and in the comparative pharmacokinetic study. Caco-2 cells were used to investigate the transport profile of paclitaxel in vitro. In the pharmacokinetic study, rats were randomly grouped and administered with T. yunnanensis extract or pure paclitaxel. The results showed that the AUC and C(max) of paclitaxel in rats receiving the T. yunnanensis extract were significantly increased than those receiving the pure paclitaxel, and the in vitro Caco-2 cell monolayer transport study found that the coexisting constituents in the extract of T. yunnanensis could inhibit the efflux of paclitaxel. These findings suggested that the oral absorption and bioavailability of paclitaxel in T. yunnanensis extract were remarkably higher when compared with the pure paclitaxel, and the coexisting constituents in the T. yunnanensis extract might play an important role for the enhancement of the oral absorption and bioavailability of paclitaxel.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Dake
authors.initials: D
authors.lastname: Cai
authors.forename: Huichang
authors.initials: H
authors.lastname: Bi
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhong
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.forename: Lianquan
authors.initials: L
authors.lastname: Gu
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D017239:Paclitaxel / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000493:pharmacokinetics*; D018515:Plant Leaves; D018547:Plant Stems; D051381:Rats; D017207:Rats, Sprague-Dawley; D020946:Taxus / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D017239:Paclitaxel
keywords: Absorption; Bioavailability; P-gp; Paclitaxel; Pharmacokinetics; Taxus yunnanensis